Augmenter of liver regeneration (ALR) is a newly discovered cytokine that can promote liver regeneration and proliferation of damaged liver cells. In the renal tissue, ALR is mainly expressed in the cytoplasm of the medullary loops, collecting ducts and distal convoluted tubules in the renal medulla, and is low in the glomerular and cortical tubules. Various stimulation, such as ischemiacal, hypoxia, poisoning and inflammatory stimulation, can induce the expression of ALR in the epithelial cells of proximal tubule regeneration and the damaged areas of cortex, and participate in the repair process. Current studies have found that in acute kidney injury (AKI), exogenous ALR can protect renal tubular epithelial cells by inhibiting apoptosis of renal tubular epithelial cells, promoting proliferation of renal tubular epithelial cells, inhibiting the activities of inflammatory cells, and promoting the reduction of renal injury. This paper intends to review the basic characteristics of ALR and the pathogenesis of AKI, summarize the characteristics of the mechanism of ALR in AKI by combing the relevant literature on ALR and AKI in recent years, and provide knowledge reserve and direction reference for the in-depth study of ALR in kidney in the future.
ObjectiveTo summarize the progress of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and evolution of surgical procedure improvement, so as to summarize experience in selecting appropriate surgical method for patients. MethodThe domestic and foreign literature on the evolution of ALPPS surgical procedure improvement in recent years was reviewed. ResultsIn the decade since the emergence of ALPPS, the ALPPS had been rapidly developed in the hepatobiliary surgery. The ALPPS promoted a rapid increase in future liver remnant during a relatively shorter period to contribute to resectability of liver tumors and reduce the rate of postoperative liver failure, the patients with intermediate to advanced and huge liver cancer could obtain the surgical radical resection. In recent years, the domestic and foreign experts had refined the ALPPS procedure, which mainly focused on the operation of hepatic section separation and hepatic artery flow restriction in stage Ⅰ surgery, including partial ALPPS, radiofrequency ablation ALPPS, tourniquet ALPPS, transcatheter arterial embolization ALPPS, hepatic artery ringed and operation ALPPS, as well as laparoscopic ALPPS and robotic ALPPS with minimally invasive approach. ConclusionsDespite the ongoing controversy over ALPPS, with the continuous progress and innovation of improved procedures and the utilization of laparoscope and robot in surgery, the trauma of ALPPS surgery has a further reduction, and the morbidity and mortality have gradually been decreased. It is believed that with the continuous advancement and improvement of ALPPS surgery technology, the indications and safety of ALPPS will be further enhanced, bringing hope to more patients with intermediate to advanced liver cancer with huge tumors.
ObjectiveTo understand the latest development in lineage tracing techniques and their applications in the study of liver regeneration mechanisms. MethodA review of domestic and international literature on the application of lineage tracing techniques in liver regeneration was conducted. ResultsA variety of more reliable and advanced lineage tracing techniques had been developed, such as single-cell RNA sequencing, DNA barcode technology, etc., providing powerful tools for a deeper understanding of the mechanisms of liver regeneration. The marked progress had been made in identifying the origins of liver regeneration cells, identifying liver regeneration areas, and studying the mechanisms of liver regeneration after injury. The lineage tracing techniques help to understand the position and function of different types of liver cells within the liver structure, revealing the regenerative potential and contribution of different subpopulations of liver cells. Moreover, these techniques had supported the phenomenon of transdifferentiation between the hepatocytes and the bile duct cells under chronic liver injury conditions, aiding in understanding the specific roles of key signaling pathways in liver regeneration, such as Wnt/β-catenin, Hippo/YAP, and Notch signaling pathways.ConclusionsAlthough lineage tracing techniques have made marked progress in liver regeneration research, liver regeneration is a complex and important physiological process, and the technique still has limitations, such as challenges in marker specificity, longer research cycles and higher costs, potential limitations in translating from animal models to human clinical applications, inability to solve all questions about liver regeneration mechanisms, and ethical and legal issues. Therefore, more in-depth and comprehensive research is still needed to reveal more details of liver regeneration mechanism.
Objective To examine the effect of zinc finger protein A20 on regeneration of small-for-sized liver allograft, graft rejection and recipient rat survival time. Methods Small-for-sized liver transplantation with 30% partial liver allograft was performed by using a b-rejection combination rat model of DA (RT1a) to Lewis (RT1l) rats. The rats were grouped into rAdEasy-A20 treatment group （A20 group）, the control empty Ad vector rAdEasy treatment group (rAdEasy group) and PS control treatment group (PS group). Ex vivo gene transfer in donor liver graft was performed through portal vein infusion. Animals were assessed for survival days, expression of A20 in liver graft, liver graft regeneration, hepatocyte apoptosis, graft rejection, NF-κB activation and ICAM-1 mRNA expression in liver graft sinusoidal endothelial cells (LSECs), number of liver graft infiltrating mononuclear cells (LIMCs) and the subproportion of NK/NKT cells, and serum IFN-γ level. Results Survival day of A20 group rats was prominently longer than that of PS group rats and rAdEasy group rats (P=0.001 8), whereas survival day of rAdEasy group rats was remarkably shorter than that of PS group rats (P=0.001 8). Regeneration of the small-for-sized liver allograft was markedly augmented by A20, BrdU labelling index of hepatocyte on postoperative day 4 was significantly increased in the A20 group compared with the PS group and rAdEasy group (P＜0.01). Hepatocyte apoptosis on postoperative day 4 was significantly inhibited by A20 (P＜0.01). On postoperative day 4, histologic examination revealed a mild rejection in the A20 group but a more severe rejection in the PS and rAdEasy groups. NF-κB activity and ICAM-1 mRNA expression in LSECs on postoperative day 1 were notably suppressed by A20 overexpression. Flow cytometry analysis showed a marked downregulation of LIMCs number by A20, including more prominent decrease in the subproportion of NK/NKT cells on postoperative day 1 and 4, respectively (P＜0.05). Serum IFN-γ level on postoperative day 4 was also significantly suppressed by A20 overexpression (P＜0.05). Conclusion These data suggest that A20 could effectively promote small-for-sized liver allograft regeneration, suppresses rejection and prolong survival days of recipient rats. These effects of A20 could be related to an inhibition of LSECs activation, suppression of infiltration of LIMCs and the subpopulations such as NK cells and NKT cells into liver graft, and inhibition of hepatocyte apoptosis.
OBJECTIVE: To validate the hemostatic properties of collagen sponge made in China. METHODS: The experimental model of superficial cut of liver was established in 20 Sprague-Dawley adult rats, which were divided into two groups randomly. Collagen sponge or gelatin sponge was used to cover the cut respectively. Hemostatic result was observed. Afterwards, standard liver trauma model by resection left front liver lobe was made, wound was treated with collagen sponge or gelatin sponge respectively. Hemostatic result was observed. Concurrent hemostatic time and bleeding amount were noted. At 7, 14 and 20 days after operation, intra-abdominal adhension, infection and healing state of liver were observed by exploratory laparotomy. The histological changes of regenerate liver tissue were observed by microscopy. RESULTS: Collagen sponge adhered to wound well. Concurrent hemostatic time and bleeding amount in collagen sponge group were superior to those of gelatin sponge (P lt; 0.05). The histological examination showed that collagen sponge was absorbed and degraded rapidly, regenerative hepatocytes could be induced. CONCLUSION: Collagen sponge has fine hemostatic properties and can induce regeneration of hepatocytes effectively. It is worth popularizing for its convenience in clinical application and its properties of rapid degradation and absorption.
ObjectiveTo evaluate the effect of heparin binding epidermal growth factor-like growth factor (HB-EGF) on liver regeneration after partial orthotopic liver transplantation. MethodsFourty SD rats were used to establish the model of partial orthotopic liver transplantation with ameliorated two-cuff technique. Then all the rats were divided into 2 groups: experiment group and control group. Twenty rats of experiment group were administered 500 μg/kg HBEGF via vena caudalis immediately after operation twice a day, while the same volume of saline was administered to the rats in control group. Five rats in each group were selected randomly and killed at the 6th hour, day 2, 4 and 7 after operation, respectively. The serum levels of albumin (Alb) and alanine aminotransferase (ALT) in the blood sample were detected. Every liver was removed and weighed. The expression of Ki67 was detected by using immunohistochemistry assay. The regeneration activity of hepatocytes was evaluated by flow cytometry. ResultsThe wet weights of liver in experiment group were all significantly higher than that in control group at the 6th hour, day 2 and 4 after transplantation (P＜0.05). The serum levels of ALT were significantly lower in experiment group than those in control group at the 6th hour, day 2， 4, 7 after operation (P＜0.05), while the levels of Alb were significantly higher on day 4 and 7. The proliferating index and Ki-67 labeling index of graft in experiment group were higher than those in control group on day 2 and 4 after transplantation （2 d: P＜0.01; 4 d: P＜0.05）. ConclusionHBEGF could promote the regeneration of rat hepatocytes after partial liver transplantation.
ObjectiveTo investigate the role of endoplasmic reticulum stress in liver regeneration after associating liver partition and portal vein ligation for staged hepatectomy (ALPPS).MethodsSeventy-two C57bl/6 mice were randomly divided into ALPPS group, portal vein ligation group (PVL group), and sham operation group (Sham group), 24 mice in each group. And then one-stage ALPPS operation, simple PVL, and sham operation will be performed. Six mice were randomized selected of the three groups on the 1st, 2nd, 4th, and 7th day after surgery, respectively, the liver weight to body weight ratio (FLR/BW) of each group was measured, and the liver tissues were taken for immunohistochemical staining to calculate the proportion of Ki-67 positive cells, Western blot was used to detect the expression levels of X-box binding protein 1 (XBP1) and inositol-requiring enzyme 1α (IRE1α) proteins.Results① FLR/BW: On the 4th day and the 7th day after operation, the FLR/BW of the Sham group, PVL group, and ALPPS group increased in sequence at the same time, and the difference between the three groups was statistically significant (P<0.05). ② Ki-67 positive cell ratio: On the 2nd day after operation, the ratio of Ki-67 positive cells in the Sham group, PVL group, and ALPPS group increased sequentially, and the difference between the two groups was statistically significant (P<0.05). On the 4th day after operation, the ratio of Ki-67 positive cells in the PVL group and the ALPPS group were still higher than that of the Sham group (P<0.05). ③ Expression levels of XBP1 and IRE1α: On the 2nd and 4th postoperative day, the expression levels of XBP1 and IRE1α in the ALPPS group were higher than those in the Sham group and the PVL group (P<0.05). On the 7th day after surgery, the expression levels of XBP1 and IRE1α in the ALPPS group were higher than those in the Sham group (P<0.05), while compared with the PVL group, the expression level of XBP1 in the ALPPS group was still higher (P<0.05).ConclusionsALPPS-induced liver regeneration is more advantageous than traditional PVL in mice. It may be attributed to the obvious endoplasmic reticulum stress activation after ALPPS leading to the up-regulation of IRE1α-XBP1 expression, which is involved in the regulation of hepatocyte cell cycle and promotes hepatocyte proliferation, thus promoting rapid liver regeneration.
Objective To summarize the research progress on the regulation of hepatic sinusoidal microenvironment to promote liver regeneration based on liver sinusoidal endothelial cells (LSECs), aiming to further clarify the mechanism of liver regeneration and provide new ideas and methods for clinical promotion of liver regeneration and prevention of liver failure. Method The basic and clinical research studies on LSECs and liver regeneration at home and abroad in recent years were searched and reviewed. Results Differentiated LSECs played an important role in liver regeneration, regulated the homeostasis of hepatic sinusoid microenvironment by paracrine and autocrine, and participated in the whole process of promoting liver regeneration, such as hepatocyte proliferation and neovascularization after acute and chronic liver injury. Conclusion In the process of liver regeneration after all kinds of acute and chronic liver injury, LSECs promote liver regeneration by regulating hepatic sinusoid microenvironment, which will provide new strategies and methods for clinical promotion of liver regeneration and prevention of liver failure after hepatectomy.
Objective To analyze and summarize the research progression of phenotypic markers of hepatic sinusoidal endothelial cell （HSEC） and its role in the development and progression of the liver diseases. Methods Databases such as PubMed， Wanfang， CNKI， etc were retrieved for the latest articles on research advance in HSEC using “hepatic sinus endothelial cell”， “liver regeneration”， and “liver disease” as key words. All of the publications about studies on relation between HSEC and liver disease were reviewed and summarized. Results HSEC with specific cytoarchitectures and phenotypic markers was initially received “the message of damage” in the process of liver regeneration， hepatic immunological tolerance， hepatic fibrosis， and liver damage. Additionally， HSEC as the first barrier not only enabled liver to be protected but also was regarded as the first alternation of liver damage. Therefore， HSEC played a great important role in the process of the onset and progression of the liver disease. Conclusions The function of HSEC is complex. How do play a role and its the mechanism is unclarified， it is needed to be further studied.